Dual-Species Interactions with Intestinal Bacteria Drive Multi-Drug Resistance in Campylobacter.

OBJECTIVES: Multidrug-resistant (MDR) Campylobacter infections are an increasing clinical concern, as rising fluoroquinolone (FQ) resistance leaves macrolides as the primary treatment option. We investigated multidrug resistance in clinical Campylobacter samples from Germany. METHODS: We analyzed 6,980 clinical isolates (2010-2022), performing phenotypic susceptibility testing and sequencing on 2,912 genomes. Cultures showing multidrug resistance were studied using scanning electron microscopy (SEM). RESULTS: We found that 453 (6%) Campylobacter samples were resistant to both FQ and macrolides. Two of the C. jejuni samples were resistant to antibiotics from ten different classes. Genome analysis revealed that these samples, despite being derived from single colonies, contained >10% Enterococcus DNA reads. SEM confirmed the presence of coccoid bacteria interspersed with spiral-shaped Campylobacter. Additional culture-based purification resulted in pure C. jejuni isolates that retained FQR but lost macrolide resistance. The presence of MDR Enterococcus spp. in the mixed samples protected C. jejuni from above-MIC (minimum inhibitory concentration) of several ribosome-targeting antimicrobials whereas pure Campylobacter were susceptible. CONCLUSIONS: The impact of microbial interactions on resistance phenotypes is poorly understood. We show that close interactions with highly resistant intestinal bacteria can induce multidrug resistance phenotypes in Campylobacter. These findings highlight that microbial context shapes antibiotic resistance and may influence treatment outcomes.